Every year many patients suffering from end-stage liver disease die of liver failure before they can receive a liver transplant because of the ongoing shortage of donor organs. This shortage is projected to worsen. Alternatives for donor organs (e.g., pig livers) would enable patients with end-stage liver failure to live longer lives.
However, previous attempts have not resulted in long-term viable transplants. Giles et al. (Transplant Proc, 1970, 2(4): p. 506-12) described the first concordant liver xenotransplant procedures, of chimpanzee livers in to children with bilary atresia; the recipients survived only hours postoperatively. Starzl et al. described further attempts using baboon livers, and modern immunosuppression regimes. 1 recipient lived 70 days, 1 died after surgery (Starzl et al., Lancet, 1993. 341(8837): p. 65-71). However, baboon livers are not ideal for a number of reasons.
First transplant attempts using pig livers demonstrated hyperacute rejection of wild type porcine livers, (Makowka et al. (Transplantation, 1995, 59(12): p. 1654-9) described a heterotopic pig to human liver transplant; the recipient experienced hyperacute rejection, and died 34 hours later. Up to 3 days survival was achieved with absorption of anti GalT antibodies (Powelson et al., Transplant Proc. 1994. 26(3): p. 1353-4). Using hDAF transgenic porcine livers, 2 Baboons survived under ICU conditions for 4/8 days; the pig liver produced Coagulation factors, delaying thrombocytopenia (4-5 days) (Ramirez et al., Transplantation, 2000. 70(7): p. 989-98). 4-7 days of survival was found in baboons with 2×GalKO/8×GalKO+CD46tg porcine xeno liver transplants: there was no hyperacute rejection, but fatal, diffuse hemorrhages were seen that were interpreted as a consequence of rapid and persistent thrombocytopenia. Eight animals were euthanized, and three died POD 6-7 (Ekser et al., Am. J. Transplant. 10: 273-285, 2010).